Labrador with terrible skin problem

"Dushichka" wrote in message
...
To say I am devastated is the understatement of the millennium. We were at
the UVHosp last July and we saw the specialist dermatologist who diagnosed
immune mediated vasculitis - treatment plan was a long course of
antibiotics and prednisolone. The pred has been on and off since.When we
saw the dermatologist it was 4 months after a cruciate repair on both
legs. They were not healing properly. The op had to be repeated, again on
both legs. This was also unsuccessful,apparently due to the high dose of
pred he was taking daily.

I am LIVID that the derm, knowing my dogs history and all the clinical
signs, did not consider the possibility of Leishmaniasis and did not test
for it. I understand that his symptoms are many, but after doing my own
research, quite frankly there is nothing else it could possibly have been.

Fast forward to two months ago -poor dogs knees creak very loudly, he is
in pain, can hardly walk still on pred so I can't give him metacam, one
leg is constantly held up, just a bloody nightmare. I had to wait for an
appointment for the Uni and went last Monday where I saw the ortho vet -he
took x-rays and the knees are totally shot -bone on bone. Massive swelling
around the joints. He aspirated some of the fluid and said he was testing
for infection with a view to *flushing * the joints, said it would ease
his pain a little. I was given Atopica and Tramadol for pain.

The following night he called me and gave me the diagnosis. Back up there
the next day for more x-rays, skin biopsies, fluid from the rest of his
joints need to be tested. He said that he had never come across a case of
it before.It is the cause of each and every one of his problems. Poly
arthritis, skin lesions, muscle wasting at the temples, nosebleeds,
everything.

I am honestly in total shock -I can hardly BELIEVE that this poor dog has
been suffering for nearly TWO YEARS and it was all due to a bite from a
sand fly. Even worse, that it was not picked up on by anyone until now. I
spoke to the vet again today and I now have to wait as it is the first
documented case of it here in Ireland(only one other, but post mortem -it
was therefore untreated) and they have to obtain a special license in
order to import the drugs he needs. I am so anxious it is unbearable.

The treatment plan is daily injections of a drug called Glucantime for 40
days(which more than likely I will have to administer) with combined
Allopurinol tablets, probably for life . This will improve his clinical
symptoms but the poly arthritis is obviously irreversible and his knees
are screwed

I know it is HIGHLY unlikely, but does anyone have any experience of
this?? I only know that it is endemic in only certain parts of the U.S and
I cannot find anyone else to talk to about it

Anyone????

Please contact me privately at and I'll send you more information that you can share with your specialist.

Kris L. Christine
said in rec.pets.dogs.health:

Please contact me privately at
and I'll send you more
information that you can share with your specialist.

Since no one has been able to help Dushichka, maybe your
information would be a good thing to share with the group
instead of going private.

--
--Matt. Rocky's a Dog.

[quote='Rocky[_2_];349667']
Since no one has been able to help Dushichka, maybe your
information would be a good thing to share with the group
instead of going private.
QUOTE]

Okay, Matt, it's coming below and is quite a lot of information.

Kris

World Small Animal Veterinary Association 2006 Congress

Ischemic Skin Disease - WSAVA 2006 Congress

Ischemic Skin Disease in the Dog
Peter J. Ihrke, VMD, DACVD
Professor of Dermatology, Chief, Dermatology Service, VMTH, Department of Medicine & Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA

A. Introduction, General Information, and Definitions

1. Vasculitis is defined as a process by which inflammation is directed against vessel walls. Microhemorrhage into surrounding tissue is a frequent sequela.

2. 'Cell poor' vasculitis or 'vasculopathy' is a subgroup of vasculitis characterized by vascular damage, vascular depletion, and only sparse inflammation. Loss of endothelial cells and thickening of the vessel wall are noted.

3. Ischemic dermatopathy is a term used to group multiple vasculopathic syndromes unified by similar clinical and histopathologic characteristics.

4. Diascopy is a useful and simple clinical tool used in the diagnosis of skin diseases with a vascular component. A clear microscope slide is pressed onto skin to determine if erythema is due to dilated blood vessels or hemorrhage into the skin. Blanching of the skin indicates that erythema is due to dilated blood vessels and inflammation. If erythematous skin does not blanch, diascopy confirms hemorrhage and suggests either vasculitis or vasculopathy.

B. Classification of Ischemic Dermatopathies

1. Canine familial dermatomyositis (DM): A juvenile onset heritable inflammatory disease of uncertain etiology affecting skin and muscle, seen predominantly in the Collie, Shetland Sheepdog, and their related cross-breeds.

2. Dermatomyositis-like disease (DM-Like): A juvenile-onset ischemic dermatopathy that is clinically and histopathologically identical to canine dermatomyositis, but in a breed without proven breed predilection, and therefore without known familial predisposition.

3. Localized post-rabies vaccination panniculitis (Post-Rabies): A localized ischemic skin disease associated with a rabies vaccination site and temporal link with the vaccination.

4. Generalized vaccine-induced ischemic dermatopathy (GVIID): A generalized ischemic skin disease with a temporal linkage with rabies vaccination, but with more severe generalized post-rabies vaccination-associated disease.

5. Generalized idiopathic ischemic dermatopathy (GIID): An adult-onset generalized ischemic dermatopathy without a correlative history indicating the likelihood of induction by a rabies vaccine reaction.

These 5 syndromes are united by very similar clinical and histopathologic similarities. Groups 1 and 2 above develop as juvenile onset disease and are clinically indistinguishable from each other. Group 3 develops as focal skin disease at the site of vaccination. Group 4 and 5 develop as generalized, more severe, and usually adult-onset skin disease. Skin disease seen with group 4 and 5 may be generalized beyond the expected distribution pattern of most cases of DM (group 1) and DM-like disease (group 2).

The term, "canine familial dermatomyositis" currently should be reserved for dogs with clinical and histopathologic evidence of a juvenile onset heritable inflammatory disease affecting skin and muscle in a breed known to be at increased risk.

(Continued below)

(CONTINUED FROM ABOVE)

C. Etiology and Pathogenesis

1. The etiology of ischemic dermatopathies is not known. Multifocal immunologic damage to blood vessels probably results in ischemic damage to the skin and other susceptible organs. Cutaneous hypoxia probably leads to follicular atrophy and other associated chronic hypoxic skin changes.

2. Post-rabies vaccination associated disease is presumed to be due to an idiosyncratic immunologic reaction to rabies antigen that partially targets vessels. Rabies viral antigen can be documented in the walls of dermal blood vessels and in the epithelium of hair follicles via immunofluorescent testing. Since this syndrome is seen predominantly in very small dogs, it is tempting to speculate that the disease may be partially linked to increased antigenic load in comparison to the body size of the dog, since the same volume of rabies vaccine is given to all dogs subcutaneously.

3. Hereditary or individual predispositions, coupled with a secondary environmental trigger have long been hypothesized for dermatomyositis in humans. Similar factors probably initiate and drive canine ischemic dermatopathy. Autoimmune and viral etiologies coupled with hereditary predilection have been postulated for dermatomyositis in humans.

4. All ischemic dermatopathies share both clinical and histopathologic features that could result from cell-poor vasculitis leading to a long-term lack of cutaneous vascular sustenance. Skin hypoxia could lead to follicular atrophy and associated chronic skin changes. Lesions that occur over bony prominences can be explained by enhanced susceptibility to trauma and lesions on distal extremities can be explained by poor collateral circulation that does not allow appropriate vascular sustenance.

5. Complement-mediated microangiopathy leading to ischemia is considered to be the pathophysiological basis of skin lesions in human dermatomyositis. Complement C5b-9 membrane attack complex has been demonstrated in small blood vessels within muscle from a dog with vaccine-induced ischemic dermatopathy and cell poor vasculitis.

D. Comparison of Clinical Features

1. Clinical features shared by all 5 subgroups of canine ischemic dermatopathy given above include alopecia with crusting and post-inflammatory, mottled pigmentary change. Hyperpigmentation is seen in breeds predisposed to enhanced pigmentation secondary to inflammation; in other breeds, hypopigmentation can occur. Erosion and ulceration occurs in more severe cases, especially if trauma, secondary infection, or coexistent pruritic disease are present.

2. Dogs with Canine familial dermatomyositis (DM) and Dermatomyositis-like disease (DM-Like) (Group 1 & 2) share identical clinical features and hence will be grouped in the discussion below.

3. Dogs with Generalized vaccine-induced ischemic dermatopathy (GVIID) & Generalized idiopathic ischemic dermatopathy (GIID) share similar clinical features and will be grouped in the discussion below. However, dogs with GVIID usually have a demonstrable focal lesion at the subcutaneous vaccine site compatible with the lesions seen with localized post rabies vaccination panniculitis. Even dogs without a correlative history of recent rabies vaccination should have likely vaccination sites checked for compatible lesions, as the focal lesions may be subtle and easily missed.

E. Histopathologic Features (Adapted from T.L. Gross)

1. The histopathologic features of all ischemic dermatopathies are similar. Diagnosis of cell-poor vasculitis relies on recognition of subtle ischemic changes in the skin. Altered staining of collagen and 'fading' atrophy of hair follicles are the most characteristic features. The epidermal and dermal changes overlying post-rabies vaccination panniculitis are identical to those seen with other ischemic dermatopathies.

2. Scattered degeneration of individual basal cells and prominent degeneration of follicular basal cells are noted.

3. Secondary dermal-epidermal vesiculation occurs in more severely affected animals. Vesicles contain red blood cells and occur above the basement membrane. Artifactual dermal-epidermal separation "usable artifact of Stannard") may occur at biopsy specimen margins.

4. Dermal inflammation consists of diffuse, mild lymphocytic and histiocytic inflammation that encircles hair follicles.

5. Diffuse pallor of dermal connective tissue with pale-staining, smudged, collagen probably results from tissue ischemia.

6. Vascular lesions are subtle. Loss of endothelial cells, mummification of small vessels, or hyaline mural alteration may be seen. Leukocytoclasia may be present.

7. Severely atrophic or faded, atrophic hair follicles may be a direct consequences of ischemia and basal cell degeneration.

8. Myositis with mixed inflammation, regeneration, fibrosis, and atrophy may be present. Random biopsy may not show muscle lesions.

9. Localized post-rabies vaccination panniculitis also shows a nodular localization of lymphocytes and other mononuclear cells in the lower dermis and panniculus. Amorphous basophilic deposits resembling vaccine product may be present.

F. Canine Familial Dermatomyositis (DM) & Dermatomyositis-like disease (DM-Like) (Group 1 & 2)

1. Signalment predilections:

a. Breeds--DM--Shetland Sheepdogs, Collies, and related crossbreeds.

b. Breeds--DM-like--Chow Chow, Beauceron Shepherds, Welsh Corgi, Lakeland Terrier, German Shepherd Dog, and Kuvasz (published). Additionally, Miniature Schnauzers, Miniature Dachshunds, Fox Terriers, and other breeds have been confirmed by Ihrke or Gross.

c. Age--both are juvenile-onset diseases; lesions usually occur by 6 months of age.

d. Sex--sex predilection has not been noted.

2. Initial lesions--rare transient papules, pustules, and vesicles eventuating in crusted erosions, ulcers, and alopecia.

3. Chronic lesions--scarring is seen with chronicity. Pigmentary aberrations give rise to poikilodermatous change with either hyper or hypopigmentation.

4. Sites--initial lesions occur over bony prominences (sites of mild trauma), especially on the muzzle; in periorbital and perioral locations; and on the dorsal paws. Similar lesions occur on distal extremities with poor collateral circulation, and on pressure points susceptible to shearing injury and trauma. The pinnal tips, pinnal folds, nail folds, tip of the tail, other bony prominences can be affected. Nail dystrophy and sloughing may be seen.

5. Pain and pruritus occur if ulceration or secondary pyoderma are present.

6. Relapse--photo-aggravation, trauma or estrus can trigger relapse.

7. Muscle involvement--subtle, may be limited to the temporal and masseter muscles. Difficulties with mastication and swallowing can occur. Concurrent clinical, electromyographic, or histologic evidence of muscle disease aids in diagnosis.

8. Severely affected dogs--growth retardation, megaesophagus, lameness, and widespread muscle atrophy. The tongue may fasciculate causing difficulty in prehension. Infertility can occur in severe dermatomyositis.

9. Diagnosis--compatible skin lesions, confirmatory skin biopsy, muscle disease.

10. Prognosis--mildly affected dogs may achieve clinical remission. Severely affected dogs with generalized disease exhibit cyclical lifelong disease.

G. Localized Post-Rabies Vaccination Panniculitis (Post-Rabies)

1. Signalment predilections:

a. Breeds--marked breed predilection for Toy & Miniature Poodles, and Bichon Frises. Shih Tzu, Lhasa Apso, Maltese, Silky Terrier, Yorkshire Terrier, Chihuahua, Toy Manchester Terrier, American Eskimo, Poodle crossbreeds, and Miniature Dachshunds also have been confirmed by Ihrke or Gross.

b. Age & sex predilections have not been noted.

2. Initial lesions--an alopecic macule or plaque develops at the site of prior subcutaneous rabies vaccine deposition. The time between vaccination and noting of the lesion usually is between one and three months. Average lesion size is 2 to 10 cm in diameter. Smaller satellite lesions may be present. A few hairs may remain within the boundaries of the lesion. Visible inflammation commonly is minimal.

3. Chronic lesions--hyperpigmentation may be an occasional sequela, especially in black Miniature Poodles and other breeds that tend to respond to inflammation by hyperpigmentation.

4. Sites--neck and shoulder region near the scapula where most subcutaneous rabies vaccinations are given. Gravitational drift may result in lesions ventral to vaccination site.

5. Systemic signs--a small subgroup of dogs display lethargy, depression, and fever. Elevated liver enzymes have been noted. Systemic signs may precede the skin lesion or occur concomitantly.

6. Diagnosis--history of vaccination, compatible skin lesions, confirmatory skin biopsy.

7. Prognosis--most lesions remain small and are asymptomatic. Exacerbation has been observed after revaccination.

H. Generalized vaccine-induced ischemic dermatopathy (GVIID) & Generalized idiopathic ischemic dermatopathy (GIID)

1. Signalment predilections:

a. Breeds--Miniature and Toy Poodle, Shih Tzu, Shetland Sheepdog, Lhasa Apso, Pomeranian, and Yorkshire Terrier may be at increased risk for both types of adult-onset generalized ischemic dermatopathy. Long-haired toy or miniature breeds seem to be at greater risk.

b. Age & sex predilections have not been noted.

2. Clinical skin lesions--individual lesions are those of DM and DM-like disease but may be more severe and more generalized. More severe lesions are located over bony prominences and on distal extremities. Similar, but usually less severe lesions are seen over much of the skin surface.

(continued below)

(continued from above)

3. Muscle atrophy--variable, but may be marked.

4. Systemic signs--some dogs with GVIID display lethargy, depression, and fever. Elevated liver enzymes have been noted. Systemic signs may precede the skin lesion or occur concomitantly.

5. Prognosis--generalized vaccine-induced ischemic dermatopathy may gradually diminish in severity over time. Dogs with GIID usually exhibit lifelong disease with some cyclical recrudescence. Revaccination can exacerbate disease.

I. Other reported Ischemic Dermatopathies

1. Other syndromes have been reported that share features with cell-poor vasculopathies and ischemic dermatopathies.

2. Reported diseases include familial cutaneous vasculopathy of German Shepherd Dogs, and cutaneous vasculitis in Jack Russell Terriers.

J. Familial Cutaneous Vasculopathy of German Shepherd Dogs

1. Familial cutaneous vasculopathy of German Shepherd Dogs is a rare vascular disease affecting predominantly the pawpads of German Shepherd Dog puppies. Pedigree analysis indicated probable autosomal recessive inheritance. Most published cases (26 dogs) were seen in Canada, with another from the United States, and another from Italy.

2. Immunologic attack on collagen has been hypothesized as a mechanism.

3. A temporal association with puppy vaccination and recrudescence with repeat vaccination was seen in some of the dogs, similar to some ischemic dermatopathies.

4. Clinical features--the prime clinical feature is depigmented, swollen pawpads. Erosions, ulceration, and hair loss with adherent crusting occur

5. Sites--pawpads are affected preferentially. Similar lesions may be present on the pinnae, tail tip, and nasal planum.

6. Other clinical signs--lymphadenopathy may occur. Systemic signs include pain, lethargy, pyrexia, and pain on ambulation.

7. Histopathologically identical lesions were seen in the pawpads of a Fox Terrier and Miniature Schnauzer with presumed ischemic lesions affecting the muzzle and ears (T.L. Gross). 'Paw pad vasculopathy' may be one manifestation of ischemic dermatopathy in some breeds. Coexistent mild skin lesions may be overlooked.

K. Cutaneous Vasculitis in Jack Russell Terriers

1. A syndrome characterized by cutaneous vasculitis has been reported in 5 Jack Russell Terriers. The most prominent histologic feature was a cell poor vasculitis.

2. The range of reported age of onset and clinical features both were wide.

3. Familial predisposition is suggested by all affected dogs being of the same breed.

4. Most likely, these cases also reflect canine ischemic dermatopathy.

L. Diagnosis & Differential Diagnosis--Overview

1. All of the ischemic dermatopathies are diagnosed by clinical features and skin biopsy. Electromyographic examination is recommended if DM or DM-like disease are suspected.

2. Clinical differential diagnoses for canine DM and DM-like disease include juvenile-onset demodicosis, dermatophytosis, facial pyoderma, and discoid lupus erythematosus.

3. The diagnosis of post-rabies vaccination panniculitis is simplified by localization to a site of prior vaccination, breed predilections, plus a temporal link to vaccination.

4. More severe cases of GVIID and GIID must be differentiated from other inflammatory diseases where extensive alopecia and pigmentary changes are seen. Differential diagnoses include other vasculitides, severe erythema multiforme and epitheliotropic lymphoma. Generalized demodicosis and generalized dermatophytosis also may resemble ischemic dermatopathy. Most cases of GVIID have a focal lesion at a prior vaccine site. Skin scrapings should be performed to rule out demodicosis and fungal culture should be performed to rule out dermatophytosis. Skin biopsy is required for definitive diagnosis.

M. Management of Ischemic Dermatopathies--Overview

1. Management of ischemic dermatopathies is challenging. Response to therapeutic manipulations can be slow and perception of response is highly subjective.

2. Minimally affected dogs require little management; the disease may be largely cosmetic.

3. Severely affected dogs are difficult to manage. Dogs with substantial concomitant muscle disease (DM & DM-like) may have difficulties in prehension and swallowing. Megaesophagus leading to aspiration pneumonia occurs in severely affected dogs.

4. Medications aimed at diminishing or preventing inflammation may be beneficial.

a. Omega-3 and Omega-6 fatty acid supplementation may offer some benefit.

b. Vitamin E (200-800 IU/day) may be beneficial.

5. Pentoxifylline (Trental®, Hoechst-Roussel), available as a 400mg coated tablet (200-400 mg/day / 10-30 mg/kg/day). The drug is a methylxanthine derivative with rheologic and immunomodulatory effects. Pentoxifylline increases red blood cell deformability, alters tissue response to multiple cytokines, and diminishes production of TNF-alpha.

6. The use of corticosteroids for the treatment of ischemic dermatopathies is controversial. Anti-inflammatory effects may be beneficial, but overuse is detrimental. Potent topical corticosteroids may diminish epidermal thickness leading to increased skin fragility. Systemic corticosteroid overuse can lead to iatrogenic hyperglucocorticoidism and highly deleterious side effects such as 'corticosteroid-induced-owner-loss-of-hope!

N. Factors Complicating Management--Adjunctive Recommendations

1. Restrict potential for cutaneous trauma--rough play with other dogs, especially puppies can lead to profound exacerbation of skin lesions.

2. Prevent self-trauma in response to concomitant skin diseases--any coexistent skin disease characterized by pruritus must be relentlessly managed long-term to prevent the cycle of self-trauma followed by further ischemic damage. The most commonly present troublesome coexistent pruritic skin diseases include flea allergy dermatitis, canine atopic dermatitis, and food allergy.

3. Secondary infection or bacterial or yeast overgrowth--either Staphylococcus or Malassezia can markedly exacerbate inflammation and pruritus and contribute to additional pruritus and self-trauma complicating management.

4. Long-term surveillance to prevent recurrence of pruritic skin diseases or secondary pyoderma and Malassezia dermatitis--surface cytologic examination looking for organism overgrowth should be performed whenever inflammation seems to be exacerbating in an ischemic dermatopathy.

5. Minimize solar exposure--sun exposure can exacerbate ischemic dermatopathies.

6. Localized demodicosis restricted to the site of the skin lesions of dermatomyositis has been noted in multiple Shetland Sheepdogs. The significance of these findings is not known, but may indicate focal aberrations in immune surveillance.

References

1. Crowson, A.N. & Magro, C.M. (1996) The role of microvascular injury in the pathogenesis of cutaneous lesions of dermatomyositis. Hum Pathol, 27, 15-9.

2. Fondati, A., Fondevila, M.D., Minghelli, A. et al. (1998) Familial cutaneous vasculopathy and demodicosis in a German shepherd dog. J Small Anim Pract, 39, 137-9.

3. Gross, T.L., Ihrke, P.J., Walder, E.J. & Affolter, V.K. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. Blackwell Scientific, 49-52, 247-250, 503-505, 538-541, 2005.

4. Ihrke, P.J. & Gross, T.L. (1993) New Thoughts on the Pathophysiology, Diagnosis, and Treatment of Alopecia in the Dog. Proceedings of the William Dick Bicentenary 1793-1993, University of Edinburgh, 89-94.

5. Kovacs, S.O. & Kovacs, S.C. (1998) Dermatomyositis. J Amer Acad Dermatol, 39, 899-920.

6. Magro, C.M., Crowson, A.N. & Regauer, S. (1996) Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease. Human Path, 27, 1, 50-6.

7. Parker, W.M. & Foster, R.A. (1996) Cutaneous vasculitis in five Jack Russell Terriers. Vet Dermatol, 7, 109-15.

8. Scott, D.W., Miller, W.H. & Griffin, C.E. (2001) Muller & Kirk's Small Animal Dermatology, 6th edn. pp. 940-6. WB Saunders Co, Philadelphia.

9. Sontheimer, R.D. (1999) Dermatomyositis. In: Dermatology in General Medicine (I.W. Freedberg, A.Z. Eisen, K. Wolff, K.F. Austen, Goldsmith L.A., & T.B. Fitzpatrick), pp. 2009-2022. McGraw-Hill, New York.

10. Vitale, C.B., Gross, T.L., & Magro C.M. (1999) Vaccine-induced ischemic dermatopathy in the dog. Vet Dermatol, 18, 131-42.

11. Weir, J.A., Yager, J.A., Caswell, J.L. et al. (1994) Familial cutaneous vasculopathy of German shepherds: Clinical, genetic and preliminary pathological and immunological studies. Can Vet J., 35, 763-9.

12. Wilcock, B.P. & Yager, J.A. (1986) Focal cutaneous vasculitis and alopecia at sites of rabies vaccination in dogs. J Am Vet Med Assoc, 188, 1174-7.


Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)
Peter J. Ihrke, VMD, DACVD
School of Veterinary Medicine
University of California
Davis, California, USA

World Small Animal Veterinary Association 2004 World Congress

Cutaneous Vasculitis and Vasculopathy - WSAVA 2004 Congress

Cutaneous Vasculitis and Vasculopathy
Verena K. Affolter
School of Veterinary Medicine, University of California, Davis
Davis, CA, USA

Introduction

Vasculitis is inflammation of the vascular wall and can occur as a primary disease, but is more commonly secondary to another concurrent disease (infections, neoplasia, connective tissue diseases, drug reactions). Vasculitis may involve only one organ system, such as the skin or may involve multiple organ systems. Cutaneous vasculitis typically results from small vessel vasculitis. Vasculitis is more often seen in dogs than in cats.

Etiology and pathogenesis

Vasculitis can be classified based on the histopathologic appearance: lack or presence of inflammatory infiltrates as well as size and type of vessels involved (small vessel vasculitis, arteritis, phlebitis). However, these classifications do not reliably correlate with a specific etiology. Most important is to differentiate between vasculitis induced by infectious pathogens and vasculitis induced by an immune-mediated process due to exogenous or endogenous antigens (Table 1). In over 50% of cases an etiology cannot be determined.

Non-immunopathogenic mechanisms--Vasculopathic effects of endotoxins or hemodynamic factors (example: cold agglutinin disease) can compromise the integrity of the vascular walls. The result is structural damage and inflammation of the vascular wall.

Immunopathogenic mechanisms may be triggered by infectious pathogens (rickettsial infections, babesiosis, leishmaniasis, feline immunodeficiency virus). Perivascular and/or intramural located infectious pathogens initiate the specific immune response and the vascular wall is damaged by the ensuing inflammation. In a similar manner, localized bacterial infections and/or septicemia can result in secondary vasculitis. Immune-mediated vasculitis is typically triggered by an adverse drug reaction (antibiotics, nonsteroidal anti-inflammatory medications, vaccines, therapeutic injections of sera and extracts of allergens for atomic dermatitis therapy) or underlying internal diseases (neoplasia, infections distant from area of vasculitis). Autoimmune diseases (connective tissue diseases such as systemic Lupus erythematosus) may be accompanied by vasculitis.

Table 1. Vasculitis classification

Infectious Vasculitis

Bacterial
bacterial endocarditis, septicemia, mycobacterial disseminated vasotropic

Fungal
fungal

Viral
Herpes virus, FIP, FIV, FeLV

Rickettsial
ehrlichiosis

Parasitic
dirofilariasis, babesiosis, leishmaniasis, trypanosomiasis

Non-Infectious Vasculitis

Exogenous antigen
drugs, food additives

Endogenous antigen
neoplasia, connective tissue diseases

Unknown antigen ("idiopathic")
sub classify according to:
--1st by vessel type, size and location
--2nd by inflammatory infiltrate


a) Deposition and formation of immune complexes (type III hypersensitivity reaction; Arthur phenomenon) is generally associated with a neutrophilic vasculitis. Immune-complexes attract complement factors and the complement cascade is initiated, with formation of the membrane attack complex (MAC). Opsonized pathogens (C3b, C4b, antibodies) are phagocytosis. C5a and leukotrienes are chemo-attractants for neutrophils and C3a, C4a, and C5a act as anaphylatoxins. Perivascular mast cell degranulate and release vasoactive amines, prostaglandins and leukotrienes and cytokines such as TNF-a. Neutrophils are recruited and degranulate, releasing various factors including lysosomal enzymes and oxygen reactive species. This results in fibrinoid necrosis of the vascular wall. In humans antineutrophilic cytoplasmic antibodies (ANCA) can be found in association with neutrophilic vasculitis.

b) Cytotoxic T cells directed against structural components of vascular walls may directly damage the vascular wall. CD8+ cytotoxic T cells can recognize haptens, such as drug metabolites, bound to components of the vascular wall, initiating immunologic reactions resulting in vasculitis.

(CONTINUED BELOW)

(continued from above)

c) Type I hypersensitivity reactions can cause an eosinophilic vasculitis (arthropod bites, insect-induced eosinophilic dermatitis). Perivascular mast cells release IL-5, which is a potent chemoattractant for eosinophils. Activated eosinophils release preformed major basic protein and eosinophilic cationic protein from cytoplasmic granules, both are toxic to tissue.

d) Vasculitis syndromes of unknown etiopathogenesis: leukocytoclastic vasculitis of the nasal region in Scottish Terriers, familial cutaneous vasculopathy of German Shepherd dogs and idiopathic septal panniculitis, proliferative arteritis of nasal philtrum (Saint Bernard), canine pinnal vasculitis.

Clinical presentation

Vasculitis may develop in any breed; Dachshunds, Rottweilers, Collies, Shetland sheepdogs and Jack Russell terriers may be predisposed. Vaccine-induced vasculitis is mainly seen in small breed dogs (Toy Poodles, Silky terriers, Yorkshire terriers, Pekingese, Maltese and Bichons). Some syndromes have been associated with specific breeds (vasculitis secondary to sulfonamide-trimethoprim therapy in Dobermans, vasculopathy in racing Greyhounds, etc).

Acute vasculitis--Legs and feet, ears, lips, tip of the tail, scrotum, and oral mucosa are mostly affected. These areas are more vulnerable as their blood supply has limited collateral circulation. With cutaneous vasculitis erythema, ecchymoses, areas of necrosis, and well-demarcated, "punched out" ulcers, and occasionally hemorrhagic bullae and/or pustules are seen. Erythema caused by vasculitis does not blanche with diascopy because of extravasation of the red blood cells. Subcutaneous vasculitis presents as nodular lesions. Systemic vasculitis causes variable clinical signs depending on the organ systems involved: phasic pyrexia, lethargy, anorexia, myalgia, arthralgia, lymphadenopathy and nasal discharge are seen. Wide spread systemic vasculitis may progress into shock and disseminated intravascular coagulation.

Chronic vasculitis--Less severe or slowly progressive vasculitis results in low-grade ischemia. Clinically these cases become evident at a chronic stage. Patchy alopecia, scaling, erythema and hyperpigmentation are seen. Lesions typically involve the pinnae, face, feet and tip of the tail often occurring over pressure points.

Diagnosis

Clinicopathologic findings--Anemia, thrombocytopenia, lymphopenia, eosinophilia, neutrophilia with a left shift and toxic changes, hypoalbuminemia, and elevated liver enzymes may be seen with systemic vasculitis. Circulating immune complexes, diminished complement factors and hypergammaglobulinemia may be present with immune-mediated vasculitis.

Evaluation for underlying infectious diseases--serial blood cultures, urine culture, serology, lymph node aspiration, heartworm antigen testing, histopathology and culture of lesional tissue are recommended.

Evaluation for an adverse drug reaction is essential. This includes drugs administered for any concurrent disorder, vaccinations, heartworm preventatives, diet and food additives, herbal supplements or homeopathic remedies.

Evaluation for underlying internal noninfectious disease--Evaluation for internal neoplasia or systemic immune disorder is indicated. This includes complete blood cell count, serum biochemistry panel, urinalysis, anti-nuclear antibody titer, arthrocentesis with evaluation of joint fluid, thoracic radiographs, and abdominal ultrasound.

Histopathology and immunohistochemistry--Inflammatory lesions of vessel walls may be subtle, focal and transient, and it may mimic leukocytic migration through the walls of capillaries and post-capillary venules.

Acute and subacute vasculitis--There are well circumscribed dermal and epidermal areas of coagulation necrosis, micro-hemorrhages, marked protein-rich edema and deposition of fibrin. The vessel walls are thickened and edematous with hyalinization and fibrinoid necrosis; the endothelial cells are swollen and necrotic (cell-poor vasculitis or vasculopathy). Degenerative changes may be associated with intramural inflammation. The presence of degenerative neutrophils, referred to as leukocytoclasia, is pathognomonic for vasculitis. Presence of inflammatory cells within arterial and venous walls indicates vasculitis, as leukocyte migration does not occur through arteries and veins. The nature of the inflammatory infiltrate may change over time. Predominantly neutrophilic vasculitis is the most common form of vasculitis; non-leukocytoclastic and leukocytoclastic (degenerative neutrophils, nuclear dusts) variants are seen. Immunohistology can identify immune complexes along vascular walls (IgG, IgM, complement). With lymphocytic vasculitis, there are tight cuffs of small CD8+ lymphocytes surrounding primarily small arterioles. It is mainly seen with chronic resolving stages of immune-complex vasculitis (vaccine-induced panniculitis, vasculopathy of German Shepherds, drug reactions). Eosinophilic vasculitis may accompany severe eosinophilic dermatitis (arthropod bite hypersensitivity, mast cell tumors). Admixed there may be marked increase of myxoid ground substance. Granulomatous vasculitis is usually a subacute to chronic stage of primary fibrinoid necrosis that may occur with neutrophilic, leukocytoclastic vasculitis. Cel-poor vasculitis or vasculopathy is the most commonly observed type of vascular change. The vascular changes may be subtle, and inflammatory cells are scant.

Affected vessel walls are thickened, hyalinized and have indistinct vessel walls and partial lack of endothelial cells. There may be deposition of PAS-positive material within the vessel walls.

Chronic vasculitis--Predominant changes are atrophy of the hair follicles ("faded follicles") and adnexal glands. The subepidermal collagen is homogenized and pale. Newly formed, arborizing thin collagen is dissecting preexisting dermal collagen. Mucin deposition may be present. The number of small dermal vessels may be decreased. The vascular walls appear thickened and hyalinized and a decrease of factor VIII+ endothelial cells is apparent. The overlying epidermis may be atrophic. Features of cell-poor interface dermatitis are common, characterized by vacuolar changes of the basal cell layer and follicular epithelium, apoptosis of basal cells and pigmentary incontinence. Larger areas of scaring may be present.

Clinical management

The clinical management with cutaneous vasculitis requires identification of the cause. Infectious etiology--appropriate antimicrobial therapy is needed. Drug reactions--all medications should be discontinued. Internal neoplasia--removal of neoplastic process is required. Immuno-suppressive therapy with glucocorticoids and possibly azathioprine or chlorambucil is often required once an infectious etiology has been ruled out. Pentoxifylline, a methylxanthine derivative, has both immunomodulatory and rheologic effects that make it a useful therapy for vasculitis. Pentoxifylline improves peripheral blood flow and decreases inflammation by decreased platelet aggregation, decreased leukocyte response to IL-1 and TNF-a and decreased production of TNF a, IL-1, IL-4, and IL-12. Patients with vasculitis will require supportive fluid therapy or nutritional support if unable to eat or drink. If there are significant areas of ulceration and necrosis, secondary antibiotic therapy may be warranted.

Examples of vasculitis

Ischemic dermatopathy in dogs: small breeds are predisposed. Primary lesion: circular patches of alopecia with perhaps mild crusting at the site of previous vaccination (may have underlying vaccine induced granuloma). Delayed secondary phase in some dogs (1-4 months): alopecia, crusting and ulceration occur on the muzzle, lips, tips and margins of the ears, tip of the tail and extremities. Etiology--A complement-induced microangiopathy is suggested (dermatomyositis in dogs and humans).

Solar induced vasculitis/vasculopathy--Severe erythema, swelling, exudation, erosions and ulcerations are limited to non-pigmented glabrous or poorly haired areas of the skin. Solar vasculopathy may develop secondarily to acquired depigmentation in diseases such as Discoid Lupus Erythematosus or after administration of photosensitizing drugs and herbs. This is mainly seen in dogs. Etiology--UV light induces formation of thymidine dimmers, increase of nitric oxide as well as damage of the DNA repair system.

Familial cutaneous vasculopathy in German Shepherd dogs--Young puppies (4-6 weeks) present with painful areas of focal depigmentation, crusting, exudation and ulceration on the nose and footpads (usually all footpads), occasionally ear and tail tips. Several puppies in a litter can be affected and the lesions often develop 7 to 10 days after first vaccination. Repeating vaccinations may exacerbate the lesions. Some puppies may be lethargic with swollen joints and pyrexia. There is no sex predilection. Biochemical parameters are normal, ANA and Coombs test are negative and peripheral lymphocyte populations within the normal range. There is a mild myeloid hyperplasic in the bone marrow. Etiology--The pattern of occurrence suggests a genodermatosis (autosomal recessive trait) with an environmental trigger (vaccine) resulting in an abnormal immunologic reaction.

Vasculitis with cartilage necrosis of the pinnal fold in dogs--Crusting, exudative, ulcerating linear lesions develop on the medial aspect of the pinna, along the fold of the ear pinna in dogs that traditionally had their ears cropped (example: Boxers). Etiology--Unknown.

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Proliferative thrombovascular necrosis of the pinna--wedge-shaped, usually bilateral symmetrical, necrosis of the distal ear pinna in dogs. Progressive syndrome, lesions are painful. Etiology--unknown.

Proliferative arteritis of the nasal planum--Saint Bernards appear predisposed. Well demarcated linear ulcers on the nasal philtrum with hemorrhage are seen. Etiology--unknown.

Septicemic vasculitis--Systemic signs are present (fever, malaise, anorexia) and rapid clinical progression is seen. Necrotizing ulcers, purpura, hemorrhagic bulla and plaques are seen. Etiology: bacterial showering derived from infections (endocarditis, pyoderma, Rocky Mountain spotted fever, ehrlichiosis, Erysipelothrix rhusiopathiae).

Idiopathic cutaneous and renal glomerular vasculopathy in racing Greyhounds--There is no sex predilection. Multiple erythematous, tender cutaneous areas of swelling, predominantly on the tarsus, stifle and inner thigh are noted. Occasionally there are lesions on the forelegs. The lesions rapidly progress to ulceration with serosanguineous discharge. In some dogs the clinical signs are limited to the skin and gradually heal. Other dogs present with skin lesions, lethargy and fever. These dogs may develop acute renal failure with azotemia, polydypsia, polyuria, vomiting, and diarrhea. Less commonly, azotemia may precede the development of cutaneous lesions. Etiology--Unknown. The syndrome has some similarities with thrombocytopenic purpura, hemorrhagic-uremic syndrome and disseminated intravascular coagulation (DIC). A strong genetic predisposition is suggested (affects only racing Greyhounds, restricted to litters or closely related litters). Cultures, special stains of skin and kidney for infectious agents and serology for rickettsial infection are negative.

Cryoglobulinemia or cold agglutinin disease--Erythema, purpura, ulcerations and punched-out necrosis, occurring predominantly on extremities. Acrocyanosis may occur. The lesions are precipitated and exacerbated by cold temperature. Etiology--Formation of auto-antibodies, which are most active at low temperatures (0-4°C). Type one cryoglobulinemia is characterized by cold reacting IgM, auto-antibodies against erythrocytes called cold-agglutinins. A second and rare type is due to non-agglutinating IgG antibodies and has been associated with lead poisoning or upper respiratory tract infections. Most cases are of unknown etiology.

Speaker Information
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Verena K. Affolter, DVM, DECVP, PhD
School of Veterinary Medicine, University of California-Davis
Davis, CA
Speaker Information:
Dr. Affolter's interests and current projects include: - Reactive histiocytosis in dogs - Histiocytomas in dogs - Progressive histiocytosis in cats - Chronic progressive swelling, hyperkeratosis and fibrosis of distal limbs in Clydesdales, Shires and Belgians suggestive of chronic lymphedema - Canine and feline cutaneous lymphocytosis - Hyperelastosis cutis in horses - Clonality in feline and canine cutaneous lymphocytosis - Density and distribution of gd-T Cells in canine skin - Density of epidermal and dermal dendritic antigen presenting cells in equine skin - Subepidermal vesicular disease in Tapirs.